The purpose of the proposed investigation is to further study the mechanism of action of drugs which are uricosuric in man, i.e. drugs which increase the urinary excretion of uric acid. Uric acid is known to be both secreted and reabsorbed by the renal tubule, although the precise locations of this transport remain to be determined. Drugs could effect either secretion or reabsorption or urate, or both. Aspirin, for example, is believed to inhibit tubular secretion of urate at low concentrations and, in addition, to inhibit urate reabsorption at high concentrations. Several studies over the years have utilized conventional physiological techniques such as stop-flow analysis and transport by kidney slices to gain rudimentary knowledge regarding urate transport and the effect of drugs on this transport. To adequately advance our knowledge of this phenomenon it is now necessary to develop biochemically oriented procedures which can provide information relating to molecular properties of urate transport. We propose to: 1) Study some kinetic parameters of uric acid transport in isolated tissue preparations, in particular in suspensions of separated proximal tubules of the rabbit and rat. 2) Isolate and study proteins in the rat and rabbit renal tubule cell which may be responsible for uric acid transport by kidney. 3) Use recently developed biochemical techniques to investigate the nature of uric acid interactions with isolated brush border membranes of the rabbit and rat. 4) Continue studies in progress in this laboratory on the interactions between uric acid and human plasma (urate binding).